Nitrile-containing compounds are highly in demand because nitrile moieties are versatile reagents for organic synthesis, as exemplified in their applications in the preparation of thiazoles, chrial 2-oxazolines, tetrazoles, 1,2-diarylimidazoles, triazolo[1,5-c]pyrimidines, and benzamidines. Compounds prepared from nitriles have properties including superoxide inhibition, ferrielectric liquid crystal dopants, antipicornaviral agents, anti-inflammatory agents, anti-asthma agents, and fibrinogen antagonists.
The use of nitriles in the preparation of thiazoles, or when reduced, thiazolines and thiazolidines, is of particular interest. Compounds such as desferrithiocin and structural analogues contain a thiazoline ring, and these compounds represent an advance in iron chelation therapy for subjects suffering from iron overload diseases. Present therapeutic agents such as desferroxamine require parenteral administration and have a very short half-life in the body, so that patient compliance and treatment cost are serious problems for subjects receiving long-term chelation therapy. Desferrithiocin and related compounds are effective when orally administered, thereby reducing patient compliance issues.
Unfortunately, 2,4-dihydroxybenzonitrile, which is a precursor to the potent, less toxic form of desferrithiocin known as 4′-hydroxydesazadesferrithiocin, remains a synthetic challenge. At this time, 2,4-dihydroxybenzonitrile is not commercially available and the related 2,4-dimethoxybenzonitrile is expensive. Therefore, there is a need for novel methods of producing 2,4-dihydroxybenzonitrile (or ethers thereof) at a reasonable cost.